J Nutr. 2006; 136(5):1287-93.
Combined Lycopene and Vitamin E Treatment Suppresses the Growth of PC-346C
Human Prostate Cancer Cells in Nude Mice.
Limpens J, Schroder FH, de Ridder CM, Bolder CA, Wildhagen MF,
Obermuller-Jevic UC, Kramer K, van Weerden WM.
BASF Aktiengesellschaft, Ludwigshafen, Germany
Epidemiologic studies have repeatedly associated a high intake of lycopene and
vitamin E with reduced prostate cancer risk. The present study examined the
ability of the 2 compounds to reduce tumor growth and prostate-specific antigen
(PSA) plasma levels in the PC-346C orthotopic mouse model of human prostate
cancer. Three days after intraprostatic tumor injection, NMRI nu/nu mice were
administered a daily oral dose of synthetic lycopene [5 or 50 mg/kg body weight
(BW)], vitamin E in the form of alpha-tocopheryl acetate (5 or 50 mg/kg BW), a
mixture of lycopene and vitamin E (5 mg/kg BW each), or vehicle. Intraprostatic
tumor volume and plasma PSA concentrations were measured at regular intervals.
Mice were killed when the tumor load exceeded 1000 mm(3) or on d 95 when the
study was terminated. Prostate and liver were analyzed by HPLC for lycopene
isomers and alpha- and gamma, delta-tocopherol concentrations. None of the
single treatments significantly reduced tumor volume. In contrast, combined
treatment with lycopene and vitamin E, at 5 mg/kg BW each, suppressed
orthotopic growth of PC-346C prostate tumors by 73% at d 42 (P < 0.05) and
increased median survival time by 40% from 47 to 66 d (P = 0.02). The PSA index
(PSA:tumor volume ratio) did not differ between experimental groups, indicating
that PSA levels were not selectively affected. Lycopene was detected only in
mice supplemented with lycopene. As in humans, most tissue lycopene was in the
cis-isomer conformation, whereas 77% trans-lycopene was used in the dosing
material. Liver alpha-tocopherol concentrations were increased in mice
supplemented with both 50 mg/kg (226%, P < 0.05) and 5 mg/kg vitamin E (41%,
P < 0.05), whereas prostate alpha-tocopherol concentrations were increased
only by the higher dose (83%, P < 0.05). Our data provide evidence that
lycopene combined with vitamin E may inhibit the growth of prostate cancer and
that PSA can serve as a biomarker of tumor response for this treatment regimen.